New method uses sound to see vividly inside living cells

A new nanoscale ultrasound technique for imaging live cells could rival the optical super-resolution techniques which won the 2014 Nobel Prize for Chemistry.(Credit: University of Nottingham)

Researchers from The University of Nottingham (UN) have developed a groundbreaking technique that uses sound rather than light to see inside live cells. The new technique provides insight into the structure and behavior of cells that could rival the optical super-resolution techniques that won the 2014 Nobel Prize for Chemistry.

The British team's new sub-optical phonon (sound) imaging technique uses shorter-than-optical wavelengths of sound, which do not carry the potentially damaging high-energy payload inherent in light. The new form of sub-optical phonon (sound) imaging provides invaluable information about the internal workings of living cells, rendered at a scale and level of detail never achieved before according to UN.

"People are most familiar with ultrasound as a way of looking inside the body — in the simplest terms we've engineered it to the point where it can look inside an individual cell," said researcher Professor Matt Clark. "Nottingham is currently the only place in the world with this capability."

Conventional optical microscopy, which uses light to see inside cells, has limitations. This is because the size of the smallest object you can see is limited by the size of the light's wavelength.

For biological specimens, the wavelength cannot be shorter than the blue-light end of the spectrum, because blue light has the shortest usable wavelength before there's a risk of damage to cells. (And even this piece of conventional wisdom – that blue light is safe for living tissue – is the subject of debate right now.)

The risk of damage is caused by the fact that light waves emit more energy as the light wave shortens.

Light wavelengths that are even shorter than blue light are moving into the ultraviolet end of the spectrum. The energy that is carried with the photons that make up ultraviolet light is so high it can damage the cells by destroying the bonds that hold the biological molecules together.

Even optical super-resolution imaging has limitations, because the fluorescent dyes it requires are often toxic and the technique requires huge amounts of light and time to observe and reconstruct an image – which is also damaging to cells.

Unlike light, sound waves do not emit damaging energy. This means the British researchers are able to use smaller wavelengths and see smaller things at higher resolutions, without damaging the cell biology.

This meets a pressing need to study important mechanical and structural information in living cells that has, until now, been beyond the reach of conventional microscopes. The technique does not require any additional stains or chemical agents to create images of the cell structure.

"A great thing is that, like ultrasound on the body, ultrasound in the cells causes no damage and requires no toxic chemicals to work," adds Professor Clark. "Because of this we can see inside cells that one day might be put back into the body, for instance as stem-cell transplants."

You can read more about the technique in the journal Scientific Reports.

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